Topical tenofovir, a microbicide effective against HIV, inhibits herpes simplex virus-2 replication.
Topical tenofovir, a microbicide effective against HIV, inhibits herpes simplex virus-2 replication.
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DOI：
10.1016/j.chom.2011.08.015
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发表时间：
2011-10-20
影响因子：
30.3
通讯作者：
Balzarini J
中科院分区：
文献类型：
--
作者：
Andrei G;Lisco A;Vanpouille C;Introini A;Balestra E;van den Oord J;Cihlar T;Perno CF;Snoeck R;Margolis L;Balzarini J
HIV逆转录酶抑制剂替诺福韦最近被制成阴道凝胶，用作杀微生物剂。在人体试验中，1%的替诺福韦凝胶可抑制39%的艾滋病毒性传播，令人惊讶的是，单纯疱疹病毒-2（HSV-2）的传播可抑制51%。我们证明，浓度达到阴道内用1%替诺福韦局部凝胶具有直接的抗疱疹活性。替诺福韦抑制HSV临床分离株在人胚胎成纤维细胞、角质形成细胞和器官型上皮3D筏中的复制，减少HSV在离体人淋巴和宫颈组织中的复制，并延迟HSV诱导的病变和局部治疗的HSV感染小鼠的死亡。活性替诺福韦代谢物抑制HSV DNA聚合酶和HIV逆转录酶。替诺福韦必须局部给药，以达到浓度，这是高于口服治疗后的全身水平，发挥这些双重抗病毒作用。这些发现表明，单一的局部治疗，如替诺福韦，可以抑制艾滋病毒及其共病原体的传播。
The HIV reverse transcriptase inhibitor tenofovir, was recently formulated into a vaginal gel for use as a microbicide. In human trials, a 1% tenofovir gel inhibited HIV sexual transmission by 39% and surprisingly herpes simplex virus-2 (HSV-2) transmission by 51%. We demonstrate that the concentration achieved intravaginally with a 1% tenofovir topical gel has direct anti-herpetic activity. Tenofovir inhibits the replication of HSV clinical isolates in human embryonic fibroblasts, keratinocytes, and organotypic epithelial 3D-rafts, decreases HSV replication in human lymphoid and cervical tissues ex vivo, and delays HSV-induced lesions and death of topically treated HSV-infected mice. The active tenofovir metabolite inhibits HSV DNA-polymerase and HIV reverse transcriptase. Tenofovir must be topically administered to achieve concentrations, which are higher than systemic levels after oral treatment, that exert these dual antiviral effects. These findings indicate that a single topical treatment, like tenofovir, can inhibit the transmission of HIV and its co-pathogens.
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影响因子：
3.7
作者：
Rohan LC;Moncla BJ;Kunjara Na Ayudhya RP;Cost M;Huang Y;Gai F;Billitto N;Lynam JD;Pryke K;Graebing P;Hopkins N;Rooney JF;Friend D;Dezzutti CS
通讯作者：
Dezzutti CS
影响因子：
3.1
作者：
Biancotto, Angelique;Brichacek, Beda;Chen, Silvia S.;Fitzgerald, Wendy;Lisco, Andrea;Vanpouille, Christophe;Margolis, Leonid;Grivel, Jean-Charles
通讯作者：
Grivel, Jean-Charles
影响因子：
30.3
作者：
Lisco, Andrea;Vanpouille, Christophe;Margolis, Leonid
通讯作者：
Margolis, Leonid
影响因子：
3.8
作者：
Tan, Darrell H. S.;Kaul, Rupert;Walmsley, Sharon L.
通讯作者：
Walmsley, Sharon L.
DOI：
10.1126/science.1193748
发表时间：
2010-09-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Abdool Karim Q;Abdool Karim SS;Frohlich JA;Grobler AC;Baxter C;Mansoor LE;Kharsany AB;Sibeko S;Mlisana KP;Omar Z;Gengiah TN;Maarschalk S;Arulappan N;Mlotshwa M;Morris L;Taylor D;CAPRISA 004 Trial Group
通讯作者：
CAPRISA 004 Trial Group